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Biomedical subjects

G B Snow

Publications and source records attributed to G B Snow.

319 records · Page 18Linked to original sources

Detection and characterization of metastatic cervical adenopathy by MR imaging: comparison of different MR techniques.

Thirty-five patients scheduled to undergo a neck dissection for squamous cell carcinoma of the head and neck were evaluated preoperatively by magnetic resonance (MR) imaging. Axial and occasionally sagittal and coronal images were obtained. To define the most reliable technique to detect cervical lymph node metastasis, we compared several MR pulse sequences with and without Gd-DTPA administration to histopathologic findings in the neck dissection specimens. T1-weighted spin echo combined with T2-weighted gradient recalled echo (GE) sequences were found to be more useful than any other combination of pulse sequences in localizing lymph nodes. On T2-weighted GE images, lymph nodes were depicted with intermediate to high signal intensity in contrast to low signal muscular and fatty tissue. Gadolinium DTPA enhanced T1-weighted GE images reliably depict central lymph node necrosis, the most specific criterion for lymph node metastasis.

Adult↗

Long-term results of concurrent polychemotherapy and radiotherapy in patients with stomal recurrence after total laryngectomy.

From 1978 through 1985, eight patients with stomal recurrence after total laryngectomy were treated with a combination of a cytotoxic regimen (vincristin sulfate, bleomycin, and methotrexate [VBM]) and radiotherapy. The essential feature of this combination is the synchronous administration of pulses of VBM and fractionated doses of external radiotherapy in order to achieve potentiation of radiotherapy. On average, four to five pulses of VBM were given. Severe mucositis is the main problem during treatment. Two patients needed nasogastric tube feeding, and treatment was carried out as an inpatient procedure. Five patients are alive with complete local remission at 7 years, 3 years, 2 1/2 years, 14 months, and 8 months after treatment. These results appear to be spectacular, even though the number of patients is small. Of the three patients who died, only one had recurrent disease around the tracheostoma. The two other patients were free of disease in the neck when they died 6 and 16 months after treatment of, respectively, lung metastases and a second primary tumor in the lung. Patients with stomal recurrence after total laryngectomy are now routinely treated with synchronous VBM and radiotherapy.

Aged↗

Survival of malnourished head and neck cancer patients can be predicted by human leukocyte antigen-DR expression and interleukin-6/tumor necrosis factor-alpha response of the monocyte.

BACKGROUND: Patients with advanced stages of head and neck cancer are often characterized by malnutrition and by an impaired immune system. Because some of the suppressed immune parameters were shown to be of prognostic importance in trauma and sepsis, we investigated whether these would also correlate with survival in head and neck cancer. METHODS: Severely malnourished head and neck cancer patients undergoing ablative and reconstructive surgery were followed prospectively and their perioperative immune parameters were related to long-term survival. RESULTS: Forty-nine patients with a preoperative weight loss of more than 10% were followed up for a period of at least 16 months after surgery. Analyses of variance revealed that preoperative human leukocyte antigen-DR (HLA-DR) expression on monocytes and endotoxin-induced production of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were different between patients who survived and patients who died. Proportional hazards identified a weight loss of more than 12%, the presence of coexistent disease, and an HLA-DR expression on monocytes below the cutoff points (mean fluorescence index < 15, peak channel index < 9) to be of significant influence on survival. CONCLUSIONS: In addition to known prognostic parameters such as tumor stage, coexistent disease, and weight loss, the immune parameters HLA-DR expression on monocytes and endotoxin-induced cytokine production may carry prognostic value in cancer patients. Immunomodulating therapies leading to improvement of these parameters might in the future lead to increased options for treatment.

Adjuvants, Immunologic↗

Lack of effect of methotrexate on human head and neck tumours transplanted in athymic nude mice.

Human head and neck tumour tissues derived from 16 different patients were transplanted in athymic nude mice. Treatment of tumour-bearing animals with methotrexate had little or no effect on the doubling time of the xenografts. Included were three tumour lines derived from patients in whom methotrexate did demonstrate antitumour activity. These results are also in contrast to clinical experience with methotrexate, showing remissions in 50% of patients with head and neck cancer. It is unlikely that this lack of effect of methotrexate is attributed to a difference in drug pharmacokinetics between man and nude mouse, since a xenografted rat tumour was found to be sensitive. With regard to possible resistance mechanisms underlying methotrexate inactivity, we found no evidence of increased dihydrofolate reductase activity in the methotrexate-insensitive human xenografts. It is possible that in this model a selection occurs favouring the outgrowth of a resistant subpopulation of tumour cells.

Animals↗

The prognostic significance of morphometry for squamous cell hyperplasia of the laryngeal epithelium.

Laryngeal biopsies of squamous cell hyperplasia with atypia were graded by means of morphometry, using five non-correlated nuclear parameters preselected with linear discriminant analysis, and were tested for their prognostic significance, in a follow-up study. Fifty-two biopsy specimens were obtained from 18 patients who were merely followed and if necessary underwent a repeated biopsy examination. The lesions of 10 patients progressed to invasive carcinoma. In 8 patients the second or further biopsies were again classified as squamous cell hyperplasia with atypia. For both groups the mean follow-up period was 7.2 years (range: 3 1/2-11). In the progressive group 73% of the biopsies were morphometrically classified as prognostically unfavourable, whereas the clinical outcome on the basis of the last biopsy was correctly predicted for 6 out of the 10 cases (mean probability: 94%), the other 4 cases were 'mis-classified', although for 3 cases with a low probability (mean: 60%). For a valuable morphometrical classification of lesions of individual patients, the results as presented are still insufficient. Morphometrical classification probabilities may be improved when the numbers of untreated patients with squamous cell hyperplasia with atypia do increase.

Adult↗

The clinical relevance of classification of squamous cell hyperplasia of the larynx by morphometry.

By means of morphometry, differentiation between the classes of laryngeal squamous cell hyperplasia can easily be performed, mutually (Kleinsasser's classification) and in comparison with normal epithelium. It is rather difficult, however, to distinguish between class II (hyperplasia and atypia) and class III (carcinoma in situ). In the group of class II lesions, two groups of patients could be differentiated: a prognostically favourable and an unfavourable group. When using a linear discriminant analysis, the two groups mentioned could be distinguished morphometrically. In histopathological examination, lesions classified as hyperplasia and atypia (class II), must also be examined with morphometry, because in this way the group at risk can be traced.

Biopsy↗

Immunoglobulin allotypes in head and neck cancer patients with multiple primary cancers.

Immunoglobulin allotypes G1m, G2m, G3m, A2m and Km were determined in patients with a single head and neck cancer and in head and neck cancer patients with multiple primary tumours. Frequencies were compared with those of healthy controls. In all 39 patients with multiple primary tumours studied, Km(1) was absent vs. 82% and 75% absence in healthy controls and patients with a single head and neck cancer, respectively. This difference is highly significant. We conclude that head and neck cancer patients lacking the Km(1) are susceptible to the development of new cancers, and therefore should be screened thoroughly for more tumours.

Head and Neck Neoplasms↗

Activity of differentiation-inducing agents and conventional drugs in head and neck cancer xenografts.

Three putative differentiation inducing agents and five conventional drugs which have been shown to be active in patients with squamous cell carcinoma of the head and neck (HNSCC), were tested for activity against HNSCC transplanted in nude mice. Drugs were administered at a maximum tolerated dose level. By testing the effect of conventional drugs the value of the nude mouse xenograft model for testing new drugs was assessed. Bleomycin as well as cisplatin showed antitumour effects in nude mice, although toxicity and thereby the effectiveness of cisplatin varied during the 5-year period in which the experiments were performed. Bleomycin caused responses in 4 out of 13 tumour lines and cisplatin, when administered at a high dose, was active in 2 out of 5 tumours. 5-Fluorouracil and cyclophosphamide were only moderately active, while methotrexate was inactive. These data indicate that the model might be of value in the detection of new anticancer drugs although it may have a tendency to underestimate the activity of some drugs. We used the nude mouse xenograft model to test the antitumour activity of three differentiation inducing agents, the polar-planar solvents hexamethylene bisacetamide (HMBA) and N,N-dimethylformamide (DMF) and the antimetabolite 5-aza-2'-deoxycytidine (5-aza-dCyd). HMBA appeared to be inactive. In contrast, DMF was active in 1 out of 4 tumour lines while 5-aza-dCyd was active in 2 out of 5 lines tested. Furthermore, the whole panel of differentiation inducers and conventional drugs was tested for antitumour activity against three HNSCC tumour lines.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetamides↗

Evaluation of new treatment methods for head and neck cancer: a challenge.

Surgery and radiotherapy are still the best local and regional treatments for the majority of head and neck cancer patients, each alone having an impressive cure rate. However, it appears that surgery and radiotherapy have reached their upper limits. To improve the results obtained by surgery and radiotherapy, combined approaches with chemotherapy or immunotherapy must be further explored. Prospective randomized trials are essential for the evaluation of the efficacy of such multimodality treatments. Although there is an increasing commitment to this type of clinical research amongst otolaryngologists/head and neck surgeons, we still lag considerably behind other surgical and medical disciplines. Broad peer support is the conditio sine qua non that prospective randomized studies will be successfully conducted in head and neck oncology. Such studies, irrespective of their outcome in terms of which treatment is best, will provide data on important issues like that of failure sites. Accurate evaluation of the magnitude of the failure problem at respectively the local, the regional and the distant level are essential for estimating the potential for gains and establishing priorities for clinical research.

Clinical Trials as Topic↗

Activity of the folate analog 10-ethyl, 10-deaza-aminopterin (10-EdAM) against human head and neck cancer xenografts.

In a previous study we established a markedly increased antitumour activity of 10-ethyl, 10-deaza-aminopterin (10-EdAM) as compared to methotrexate (MTX) when tested in vitro in squamous cell carcinoma cell lines from the head and neck (HNSCC). In this paper we describe the antitumour activity of these drugs in vivo in athymic nude mice bearing HNSCC xenografts. Using a schedule of 125 mg/kg i.p. for both drugs, injected on day 0 and 7, 10-EdAM caused a significant response in 2 out of 5 tumour lines, whereas MTX was completely inactive. These two lines moderately sensitive to 10-EdAM were not affected when the drug was given daily times 5 at an equitoxic dose of 0.75 mg/kg, indicating that the effect of the drug may be schedule dependent.

Aminopterin↗

Serum proteinase activities in head and neck squamous cell carcinoma patients.

Proteinases are known to be involved in carcinogenesis, and various substrates are now available to measure the activity of these enzymes. No suitable serum tumour marker for head and neck squamous cell carcinoma (HNSCC) exists at this moment. Therefore, we compared proteinase-activity in serum of 20 untreated HNSCC patients with that of 20 non-cancer individuals. When N-benzoyl-DL-arginine-beta-naphtylamide (BANA) was used as the substrate, proteinase-activity seemed higher among patients, but this difference disappeared after adjustment for alcohol and tobacco consumption. Applying N-a-benzoyloxycarbonyl-L-arginyl-L-arginine-7-amido-4-methylcou marine (ZAAM) as the substrate no difference was found. Addition of E-64, an inhibitor of cysteine proteinase showed that cathepsin B contributed minimally to the ZAAM-specific activity.

Adult↗

Squamous cell carcinoma-associated antigens used in novel strategies for the detection and treatment of minimal residual head and neck cancer.

The improvement of detection and eradication of minimal residual disease, to reduce local and distant relapse after primary therapy, is one of the major challenges in the management of squamous cell carcinoma of the head and neck (HNSCC). This paper describes perspectives arising from the use of monoclonal antibodies (MAbs) E48 and U36 directed against HNSCC-associated antigens, and the molecular characterization of these antigens. Novel strategies for the detection of minimal residual disease are outlined and comprise the use of immunocytochemistry in combination with automated image analysis, and the use of an E48-specific reverse transcriptase-polymerase chain reaction (RT-PCR) method. These methods have potential for the detection of single HNSCC cells in lymph nodes, bone marrow and peripheral blood, and may contribute to the better staging of head and neck cancer in the near future. Besides this, preclinical and clinical data on HNSCC targeting with radiolabelled MAbs E48 and U36 are summarized, illustrating the perspectives of systemic adjuvant radioimmunotherapy with these MAbs.

Antigens, Neoplasm↗